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Genetic analysis of multiple synchronous lesions of the colon adenoma–carcinoma sequence
- Source :
- British Journal of Cancer
- Publication Year :
- 2000
- Publisher :
- Springer Science and Business Media LLC, 2000.
-
Abstract
- The colorectal adenoma–carcinoma sequence represents a well-known paradigm for the sequential development of cancer driven by the accumulation of genomic defects. Although the colorectal adenoma–carcinoma sequence is well investigated, studies about tumours of different dignity co-existent in the same patient are seldom. In order to address the distribution of genetic alterations in different lesions of the same patient, we coincidently investigated carcinomas, adenomas and aberrant crypt foci in patients with sporadic colon cancer. By utilizing polymerase chain reaction, single-strand conformation polymorphism, heteroduplex-analysis, restriction fragment length polymorphism, protein truncation test and sequencing techniques we looked for mutations and microsatellite instability of APC, H- ras, K- ras, p53, DCC and the DNA repair genes hMLH1/hMSH2. In accordance with the suggested adenoma–carcinoma sequence of the colon, four patients reflected the progressive accumulation of genetic defects in synchronously appearing tumours during carcinogenesis. However, two patients with non-hereditary malignomas presented different genetic instabilities in different but synchronously appearing tumours suggesting non-clonal growth under almost identical conditions of the environment. Thus, sporadically manifesting multiple lesions of the colon were not necessarily driven by similar genetic mechanisms. Premalignant lesions may transform into malignant tumours starting from different types of genetic instability, which indicates independent and simultaneous tumorigenesis within the same organ. © 2000 Cancer Research Campaign
- Subjects :
- Adenoma
Adult
Male
Cancer Research
Pathology
medicine.medical_specialty
DNA Repair
Colorectal cancer
Colon Adenoma
DNA Mutational Analysis
Adenocarcinoma
Biology
medicine.disease_cause
Neoplasms, Multiple Primary
medicine
Humans
Genes, Tumor Suppressor
Aged
Microsatellite instability
Cancer
Regular Article
Single-strand conformation polymorphism
Middle Aged
medicine.disease
digestive system diseases
adenoma–carcinoma sequence
colon cancer
Oncology
Colonic Neoplasms
microsatellite instability
Female
aberrant crypt foci
mutation
Carcinogenesis
carcinogenesis
Precancerous Conditions
Microsatellite Repeats
Aberrant crypt foci
Subjects
Details
- ISSN :
- 15321827 and 00070920
- Volume :
- 82
- Database :
- OpenAIRE
- Journal :
- British Journal of Cancer
- Accession number :
- edsair.doi.dedup.....f48b729e43de115697538e6b7a539f33